Duloxetine compared with fluoxetine and venlafaxine: use of meta-regression analysis for indirect comparisons

BACKGROUND: Data comparing duloxetine with existing antidepressant treatments is limited. A comparison of duloxetine with fluoxetine has been performed but no comparison with venlafaxine, the other antidepressant in the same therapeutic class with a significant market share, has been undertaken. In the absence of relevant data to assess the place that duloxetine should occupy in the therapeutic arsenal, indirect comparisons are the most rigorous way to go. We conducted a systematic review of the efficacy of duloxetine, fluoxetine and venlafaxine versus placebo in the treatment of Major Depressive Disorder (MDD), and performed indirect comparisons through meta-regressions. METHODS: The bibliography of the Agency for Health Care Policy and Research and the CENTRAL, Medline, and Embase databases were interrogated using advanced search strategies based on a combination of text and index terms. The search focused on randomized placebo-controlled clinical trials involving adult patients treated for acute phase Major Depressive Disorder. All outcomes were derived to take account for varying placebo responses throughout studies. Primary outcome was treatment efficacy as measured by Hedge's g effect size. Secondary outcomes were response and dropout rates as measured by log odds ratios. Meta-regressions were run to indirectly compare the drugs. Sensitivity analysis, assessing the influence of individual studies over the results, and the influence of patients' characteristics were run. RESULTS: 22 studies involving fluoxetine, 9 involving duloxetine and 8 involving venlafaxine were selected. Using indirect comparison methodology, estimated effect sizes for efficacy compared with duloxetine were 0.11 [-0.14;0.36] for fluoxetine and 0.22 [0.06;0.38] for venlafaxine. Response log odds ratios were -0.21 [-0.44;0.03], 0.70 [0.26;1.14]. Dropout log odds ratios were -0.02 [-0.33;0.29], 0.21 [-0.13;0.55]. Sensitivity analyses showed that results were consistent. CONCLUSION: Fluoxetine was not statistically different in either tolerability or efficacy when compared with duloxetine. Venlafaxine was significantly superior to duloxetine in all analyses except dropout rate. In the absence of relevant data from head-to-head comparison trials, results suggest that venlafaxine is superior compared with duloxetine and that duloxetine does not differentiate from fluoxetine

Conformational analysis of asperlin by NMR spectroscopy and molecular modeling

NOESY experiments and computerised molecular modeling have been employed to examine the configuration and conformation of the epoxypropyl side chain of asperlin in benzene solution. The data support the conclusion that the oxirane ring in this molecule has the 6S,7R configuration. Moreover, the 3J(H-5,H-6) coupling constant about the C-5-C-6 bond has been calculated using an equation suitable for the H-5-C-5-C-6-H-6 segment. This value does not support a single conformation, but rather conformational averaging that provides good agreement between the theoretical and experimental parameters

NMR spectra of aldobiuronic and aldotriuronic acid derivatives related to 4-0-methyl-D- glucuorono-D-xylans

International audienc

Synthesis and Ruthenium Coordination Complexes of the Chelating Phosphine Phosphonium-1-indenylide 1,1-Bis(diphenylphosphino)methane-1-indenylide,1-C9H6Ph2PCH2PPh2

Bis(diphenylphosphino)methane-1-indenylide, 1-C9H6PPh2CH2PPh2 (1-C9H6dppm, I), has been synthesized and characterized by NMR spectroscopy and X-ray crystallography. I reacts with [CpRu-(MeCN)3]PF6 to form the conventional sandwich complex [CpRu(η5-I)]PF6 (II), which contains a dangling −PPh2 group. Complex II isomerizes to the 18-electron species IIIc, in which the dangling −PPh2 group coordinates to the ruthenium, forcing slippage of the five-membered ring to an unanticipated 1,9,8-η3-exo mode of coordination

Remarkable reactions and intermediates in titanocene(IV) chemistry: migratory insertion reactions of 2,2-disubstituted-1-alkenes, intramolecular 1,5-σ bond metathesis via ε-agostic interactions, and a rare example of a β-agostic alkyltitanocene complex

The compound Cp(2)TiMe(2) reacts with [Ph(3)C][B(C(6)F(5))(4)] in CD(2)Cl(2) at 205 K to give, inter alia, [Cp(2)TiMe(CD(2)Cl(2))][B(C(6)F(5))(4)]. This solvent-separated ion pair reacts in turn with 2,4-dimethyl-1-pentene (DMP) to give a series of cationic species, the first being the alkene complex [Cp(2)TiMe(DMP)](+), which undergoes ready migratory insertion to form the σ-alkyl complex [Cp(2)Ti(CH(2)CMe(2)CH(2)CHMe(2))](+). The latter, which does not contain a β-hydrogen atom, rearranges rapidly via an unprecedented 1,5-σ bond metathesis reaction involving two isomeric ε-agostic species to give the σ-alkyl species [Cp(2)Ti(CH(2)CHMeCH(2)CMe(3))](+); this does contain a β-hydrogen atom and, in concurrent processes, eliminates H(2) or 2,4,4-trimethyl-1-pentene (a major product) to form respectively the allylic complex [Cp(2)Tiη(3)-(CH(2))(2)CCH(2)CMe(3)](+) (a major product) or the hydride complex [Cp(2)TiH](+). The latter reacts reversibly with free DMP to give the insertion product [Cp(2)Ti(CH(2)CHMeCH(2)CHMe(2))](+) (V, a major product), in which the italicized hydrogen atom engages in a β-agostic interaction with the metal atom. Compound V is a rare example of both a β-agostic derivative of a group 4 metallocene and a β-agostic compound of any metal in which the (1)H resonance of the agostic hydrogen can be identified in the (1)H NMR spectrum (δ -3.43). Interestingly, a NOESY experiment on V indicates slow mutual exchange between the agostic hydrogen atom, the hydrogen atoms on C(1), and those of Me(2). These observations are consistent with the intermediacy of the allylic dihydrogen species [Cp(2)Ti(H(2))η(3)-(CH(2))(2)CCH(2)CHMe(2)](+), which loses H(2) to form [Cp(2)Tiη(3)-(CH(2))(2)CCH(2)CHMe(2)](+) (a minor product). Support for all steps of the proposed reaction scheme comes from product distributions, from labeling studies utilizing [Cp(2)Ti(CD(3))(CD(2)Cl(2))](+), and from extensive DFT calculations. The observed titanocene-based chemistry stands in stark contrast to that of the analogous zirconium system, in which the unusual but well-characterized cationic methyl alkene complex [Cp(2)ZrMe(DMP)](+) does not undergo migratory insertion and subsequent reactions